The field of the present invention is sputtering metal ion lasers, and more particularly compact, low power consumption, low cost sputtering metal ion lasers which emit at wavelengths from the deep ultraviolet near 200 nm to the mid-infrared near 2000 nm.
The background for and disclosure of the invention are explained with reference to the following patents and publications each of which is hereby incorporated by reference as if set forth in full herein:
(1) Milofsky, R. E. and E. S. Yeung, xe2x80x9cNative Fluorescence Detection of Nucleic Acids and DNA Restriction Fragments in Capillary Electrophoresisxe2x80x9d, Anal. Chem., vol. 65, (1993): pp. 153-157;
(2) Chi, Z., X. G. Chen, J. S. W. Holtz and S. A. Asher, xe2x80x9cUV Resonance Raman-Selective Amide Vibrational Enhancement: Quantitative Methodology for Determining Protein Secondary Structurexe2x80x9d, Biochemistry, Vol. 37, (1988): pp. 2854-2864;
(3) Thomas, G. J., Spectroscopy of Biological Systems, Ed. Clark, R. J. and R. E. Hester, John Wiley (1986);
(4) Cho, N., Song, S., and S. A. Asher, xe2x80x9cUV Resonance Raman and Excited-State Relaxation Rate Studies of Hemoglobinxe2x80x9d, Biochemistry, Vol. 33, (1994): pp. 5932-5941;
(5) Cho, N., and S. A. Asher, xe2x80x9cUV Resonance Raman and Absorption Studies of Angiotensin II Conformation in Lipid Environmentsxe2x80x9d, Biospectroscopy, Vol. 2, (1996): pp. 71-82;
(6) Chronister, E. L., Corcoran, R. C. Song, L., and El-Sayed, M., Proc. Nat""l Acad. Sci. (USA), Vol. 83, (1986): pp. 8580-8583;
(7) Barry, B., and R. A. Mathies, Biochemistry, Vol. 26, (1987): pp. 59-64;
(8) Asher, S. A., Methods in Enzuymology, Vol. 76, (1981): pp. 371-383;
(9) Spiro, R. G., Biological Applications of Raman Spectroscopy: Vol. II, John Wiley (1987);
(10) Asher, S. A., Ann. Rev. Phys. Chem., Vol. 39, (1988): pp. 537-542;
(11) Asher, S. A., Johnson, C. R. and J. Murtaugh, Rev. Sci. Instr. Vol. 54, (1983): pp. 1657-1659;
(12) Asher, S. A., Anal. Chem., Vol. 65, No.4, (Feb. 15, 1993): pp. 201-210.
(13) Gerstenberger, et al., xe2x80x9cHollow Cathode Metal Ion Lasersxe2x80x9d, IEEE J. Quantum Elect., vol. QE-16, No. 8, (August 1980): pp. 820-834;
(14) U.S. Pat. No. 4,641,313, entitled xe2x80x9cRoom Temperature Metal Vapour Laserxe2x80x9d, to Tobin;
(15) McNeil, et al., xe2x80x9cUltraviolet Laser Action From Cu II in the 2500-A Regionxe2x80x9d, App. Phys. Letters, vol. 28, No. 4, (Feb. 15, 1976): pp. 207-209;
(16) Warner, et al., xe2x80x9cMetal-Vapor Production by Sputtering in a Hollow-Cathode Discharge: Theory and Experimentxe2x80x9d, J. App. Phys., vol. 50, No. 9, (September 1979): pp. 5694-5703;
(17) Solanki, et al., xe2x80x9cMultiwatt Operation of Cull and AgII Hollow Cathode Lasersxe2x80x9d, IEEE J. Quant. Elect., vol. QE-16, No.12, (December 1980): pp.1292-1294.
(18) Arslanbekov, et al., xe2x80x9cSelf-consistent Model of High Current Density Segmented Hollow Cathode Dischargesxe2x80x9d, J. App. Phys., vol. 81, No. 2, (January 1997): pp. 1-7;
(19) U.S. Pat. No. 5,311,529, entitled xe2x80x9cLiquid Stabilized Internal Mirror Lasersxe2x80x9d, to Hug; and
(20) U.S. Pat. No. 4,953,176, entitled xe2x80x9cAngular Optical Cavity Alignment Adjustment Utilizing Variable Distribution Coolingxe2x80x9d, to Ekstrand.
Existing lasers which emit in the deep ultraviolet between 200 nm and 300 nm have serious limitations in one or more of the following: (1) the selection of emission wavelengths, (2) average or instantaneous output power, (3) power consumption, (4) reliability, (5) size, (6) weight, and (7) cost. Because laser sources without these limitations have never been developed and commercialized, a wide range of commercial analytical instrumentation that could benefit from such sources have never been enabled.
Capillary electrophoresis, high performance liquid chromatography, laser-induced fluorescence, fluorescence microscopy, and Raman spectroscopy are emerging as powerful analytical tools for a wide range of biological and chemical research. In addition, these instrumental techniques are being increasing used in commercial applications such as product inspection during the manufacture of pharmaceutical and medical products, manufactured food products and other chemical products.
Capillary electrophoresis (CE) allows rapid separation of complex chemical and biochemical mixtures and concentration of specific analytes. Laser induced fluorescence (LIF) allows the sensitive detection of analytes. Raman spectroscopy (RS) allows a high level of chemical specificity. The sensitivity and selectivity of these analytical instruments are today considerably enhanced when combined with a laser, which emits in the deep UV between 200 nm and 300 nm. The principle limitation to widespread commercial use of these systems is lack of commercially suitable UV lasers, particularly associated with limitations in emission wavelengths, duty cycle, size, power consumption, complexity, cost and reliability of existing lasers. A need exists in these fields for improved laser systems, particularly in the deep UV, that overcome these disadvantages either singly or in combination.
Capillary electrophoresis (CE) allows rapid separation of complex chemical and biochemical mixtures. Laser induced fluorescence (LIF) allows the sensitive detection of analytes. Raman spectroscopy (RS) allows a high level of chemical specificity. The sensitivity and selectivity of these analytical instruments are today considerably enhanced when combined with a laser, which emits in the deep UV between 200 nm and 300 nm. The principle limitation to widespread commercial use of these systems is lack of commercially suitable UV lasers, particularly associated with limitations in emission wavelengths, duty cycle, size, power consumption, complexity, cost and are liability of existing lasers. A need exists in these fields for improved laser systems, particularly in the deep UV, that overcome these disadvantages either singly or in combination. fluorescent labels limits the types of molecules which can be studied, reduces CE""s ability to find unexpected analytes in complex systems, may perturb the very cellular chemistry being studied, and can reduce overall sensitivity. A sensitive native CE/LIF detection method for nucleic acids and DNA restriction fragments has already been demonstrated as described in reference (1) by Milofsky and Yeung in 1993. Both the 275.4 nm line of an argon ion laser and the 248 nm line from a waveguide KrF laser were able to excite native fluorescence in the nucleic acids with a few mW of laser power. Detection limits for guanosine and adenosine monophosphate of 1.5xc3x9710xe2x88x928 and 5xc3x9710xe2x88x928 M, respectively, were as much as three orders of magnitude lower than UV fluorescent tag detection. However, the complexity and cost of the laser employed severely restrict the general utility of this technique. A need exists in this field for improved laser systems with reduced complexity and/or cost to make practical the above noted applications.
Raman spectroscopy has been demonstrated as a uniquely important technique for analyzing biological structure and function. Traditional Raman spectroscopy has been used to study a wide range of biological molecules such as protein secondary structure, nucleic acid folding and membrane phase transitions as described in reference (2) by Chi, et al., 1988. Most of this work has examined purified chemical systems, such as polymers, proteins, and nucleic acid systems, but a number of studies have probed complicated systems such as industrial and environmental samples, as well as DNA structure in whole viruses as described in reference (3) by Thomas, 1986.
The aromatic ring structures of tyrosine, tryptophane, and phenylalanine offer excellent LIF and UV resonance Raman (UVRR) cross-sections. The abundance of these three targets in the vast majority of proteins has made possible such investigations as the determination of protein acid denaturation using UVRR, characterization of excited-state relaxation rates in hemoglobin as described in reference (4) by Cho, et al., 1994, and elucidation of the secondary structure of angiotensin 11 as described in reference (5) by Cho, et al., 1996.
Resonance Raman excitation results in scattering cross-sections that are enhanced by as much as eight orders of magnitude over normal Raman spectroscopy. Resonance Raman sensitivity is comparable to that of fluorescence. Selectivity can be greater than fluorescence because Raman spectra have higher information content. Narrow Raman emission bands carry a great deal more information on molecular structure, in contrast to broadband fluorescence emission. It also allows selective study of specific chromophoric segments of a macromolecule. Visible wavelength resonance Raman spectroscopy has been uniquely incisive in the development of the understanding of energy transduction in rhodopsin and bacteriorhodopsin as described in reference (6) by Chronister, et al., 1986 and in reference (7) by Barry et al., 1987. It has also been incisive in structural and dynamical studies of numerous heme proteins such as hemoglobin and cytochrome oxidase as described in reference (8) by Asher, 1981 and in reference (9) by Spiro, 1987. However, detection of the Raman signal is usually complicated by the presence of background fluorescence from not only the molecules of interest but also from solvents and impurities.
More than ten years ago, instrumentation was developed which allowed excitation in the UV absorbing bands of molecules as described in references (10) by Asher, 1988 and in reference (11) by Asher et al., 1983. These fundamental studies have shown that unique information is available from UV resonance Raman studies of macromolecular structure. In addition, it has been shown that the ubiquitous fluorescence, which is a major impediment for visible wavelength Raman studies, does not occur for UV spectral studies below 260 nm. This is because at these high energies the excited state of most molecules in a condensed phase relaxes by means of fast radiationless processes before it has time to fluoresce as described in reference (12) by Asher, 1993.
As described above, deep UV laser radiation is useful for a wide range of commercially valuable applications. A key feature impeding the commercial development of these applications is the lack of availability of a deep UV laser of suitable cost, size, weight, power consumption and optical output properties. Thus, a need exists in these arts for a laser device that fulfills one or more of these deficiencies.
Sputtering Metal Ion Lasers
Metal ions such as those of copper, silver, and gold can provide a rich array of possible laser emission wavelengths as described in reference (13) by Gerstenberger, 1980. The historical difficulty in developing useful metal ion lasers has been associated with the method of generating an adequate metal vapor density within the gain region of the laser. Direct vaporization by evaporation or sublimation requires very high temperatures, typically about 1500xc2x0 C. for copper. Operation of lasers at these temperatures requires very high power consumption and is a major source of unreliability. In addition, in positive column discharge configurations of these lasers, insufficient population of high-energy states of copper or gold is developed to enable output at the deep ultraviolet emission lines.
A method of providing adequate metal vapor densities at lower operating temperature is through the use of volatile compounds of the metal such as a metal halide as described in reference (14) by Tobin. These types of metal ion lasers still require substantial heating of the volatile metal compound, to temperatures near 300xc2x0 C. instead of 1500xc2x0 C. However, in addition, there is a further limitation of these lasers due to the limited range of metals that can be combined into these suitable compounds. A further limitation of these lasers is that the self-terminating transitions described by Tobin only operate with very short pulse widths, making them undesirable for many biological applications.
One way to avoid these limitations is by the use of sputtering to achieve the desired metal ion densities. Sputtering metal ion hollow cathode lasers have been demonstrated in several laboratories starting about 1976, as described in reference (15) by McNeil, (16) by Warner, (17) by Solanki and up to the present time as described in reference (18) by Arslanbekov, et al., 1997. An advantage of the sputtering method of providing metal vapor is that this can be done at room temperature, thus avoiding the power requirements and warm-up time associated with the other metal vapor lasers noted above. These lasers have demonstrated the ability to provide emission over a wide range of wavelengths from about 200 nm in the deep UV to nearly 2000 nm in the middle infrared. Threshold for lasing varies considerably from laser line to laser line, but typically ranges from about 2A to 40A at 250V to 500V. Thus the input power to achieve threshold varies from about 500 W to 10,000 W.
Sputtering metal ion hollow cathode lasers described in the literature have several problems that limited their commercial use. These limitations are summarized as: too costly to manufacture both the laser plasma tube and power supply, too large, too fragile, poor lifetime and overall reliability, limited variety of laser emission lines, and limited variety of laser output performance characteristics.
Hollow cathode sputtering metal ion lasers used laser plasma tubes that were sealed on each end either with Brewster angle windows or laser mirrors. For tubes sealed with Brewster angle windows, the laser mirrors were mounted external to the laser tube. When laser mirrors were used to seal the ends of the laser tube, the critical reflecting surfaces of the mirrors were internal to the hermetic envelope of the laser plasma tube. In both cases, the structure used to maintain laser mirrors in alignment with respect to each other and with respect to the laser tube was external to the laser tube. This external structure is referred to as the external resonator structure.
In addition prior hollow cathode sputtering metal ion lasers utilized bulky, expensive, unreliable, and fragile designs for cathodes, cathode supports, and other tube design elements which made these lasers susceptible to arcing, gas clean up, and other failure mechanisms within the laser. Laser tubes of the prior art used epoxy to seal Brewster windows or mirrors. Power supplies used with these lasers were bulky, expensive, and employed designs which were not compatible with suppression of arcing within the laser tube.
For the reasons noted above, and in particular for use in the applications noted above, a need exists for lasers having one or more of reduced size, reduced weight, reduced power consumption, less restrictive cooling requirements, increased reliability, decreased cost of manufacture, and/or operation in combination with appropriate output wavelengths, appropriate instantaneous output power, and appropriate average output power.
It is a first objective of this invention to provide a sputtering metal ion hollow cathode laser for use in analytical instrumentation.
It is a second objective of the invention to create a sputtering metal ion hollow cathode laser which has low power consumption, preferably less than 500 hundred watts.
It is a third objective of this invention to create a sputtering metal ion hollow cathode laser that is compact and lightweight, preferably nearly as compact and lightweight (e.g. no more than twice the size or weight) and more preferably as compact and lightweight, and most preferably more compact and of lighter weight than a 25 milliwatt helium-neon laser.
It is a fourth objective of this invention to create a sputtering metal ion hollow cathode laser that is preferably nearly as inexpensive (e.g. no more than twice the price), and more preferably as inexpensive and most preferably less expensive than a 25 milliwatt helium-neon laser.
It is a fifth objective of the invention to create a sputtering metal ion hollow cathode laser that can emit at one or more simultaneous wavelengths in the deep ultraviolet between about 200 nm and 300 nm.
It is a sixth objective of the invention to provide a sputtering metal ion hollow cathode laser with enhanced ruggedness and dependability, preferably as rugged and dependable, and most preferably more rugged and dependable than a 25 milliwatt helium-neon laser.
It is a seventh objective of this invention to create a sputtering metal ion hollow cathode laser that emits in the near infrared between about 700 nm and about 2000 nm, and more preferably between about 700 nm and about 900 nm.
A first aspect of the invention provides an analytical instrument which includes (a) a holder for holding a sample to be analyzed; (b) a source of radiation producing a narrow band of wavelengths; (c) at least one element for causing the radiation to be incident on the sample; and (d) a detection system for detecting selected radiation resulting from interaction between the incident radiation and the sample. The source of radiation includes (1) a hollow cathode having an inner surface at least partially surrounding an opening; (2) an anode spaced from the cathode; (3) a hermetic envelope enclosing a buffer gas and the opening; (4) a first mirror having a high reflective surface, wherein the high reflective surface is at least partially within the hermetic envelope; (5) a second mirror having a partially transmitting surface, wherein the partially transmitting surface is at least partially within the hermetic envelope; (6) an optical axis defined by the first mirror and second mirror and extending through the opening; and (7) a source of electric power connected to the anode and cathode for forming an optical gain medium within the opening.
A second aspect of the invention provides a sputtering metal ion hollow cathode laser system for use in an analytic instrument that analyzes chemical composition or structure of a sample. The system includes a radiation source as noted above in association with the first aspect of the invention. The beam produced by the radiation source is used in the analytic instrument.
A third aspect of the invention provides a sputtering metal ion hollow cathode laser system similar to the radiation source as noted above in association with the first aspect of the invention. Additionally the optical axis is fixed and maintained in position by the hermetic envelope.
A fourth aspect of the invention provides a sputtering metal ion hollow cathode laser system similar to the radiation source as noted above in association with the first aspect of the invention. Additionally, the first mirror and second mirrors are bonded to the envelope using a substantially non-permeable sealing material.
A fifth aspect of the invention provides a sputtering metal ion hollow cathode laser system similar to the radiation source as noted above in association with the first aspect of the invention with the addition of the inner surface of the hollow cathode including at least two different metals.
A sixth aspect of the invention provides a sputtering metal ion hollow cathode laser system similar to the radiation source as noted above in association with the first aspect of the invention. Additionally, the electric potential provides the cathode with a cathode potential and the anode with an anode potential. Additionally, at least one dielectric material has a surface which is in the hermetic envelope and separates at least one conducting surface at the cathode potential from at least one conducting surface at the anode potential. Furthermore, a contact region between the surface of the at least one dielectric and a partially opposing surface of the at least one conducting surface at the cathode potential is located at an end of an undercut region.
A seventh aspect of the invention provides a sputtering metal ion hollow cathode laser system similar to the radiation source as noted above in association with the first aspect of the invention. Additionally, at least one of the first mirror and second mirror are provided with a coating that enhances emission of the at least one desired wavelength or suppresses emission of at least one undesired wavelength.
An eighth aspect of the invention provides a sputtering metal ion hollow cathode laser system similar to the radiation source as noted above in association with the first aspect of the invention. Additionally, the source of electric power provides modulated electric power to the cathode and anode such that part of the time an optical gain of the laser is above a lasing threshold and such that part of the time the optical gain of the laser is below the threshold.
Additional aspects of the invention provide methods of producing laser radiation that are counterparts to the system aspects noted above. Further aspects of the invention provide methods of using the produced laser radiation.
Further objectives and aspects of the invention will be apparent to those of skill in the art upon review of the detailed description of embodiments to follow. Finally it is an objective of the invention to achieve the above noted objectives alone or in combination and to provide the above noted aspects alone or in combination.